When Annette Funicello debuted on a new children’s variety TV show called the Mickey Mouse Club, she was a shy 12-year-old girl -- an unknown with big brown eyes and a sweet smile.

But the Mickey Mouse Club quickly became a television megahit and the girl known simply as “Annette” became the most popular “Mouseketeer” on the show, attracting fans all around the world. She developed into a stunning young woman, starring in several iconic, beach movies with teen heartthrob Frankie Avalon.

But in 1992 at age 50, Annette went public with devastating news -- she had multiple sclerosis, a debilitating neurological disorder. She had the most severe form of the disease and over the years lost her ability to walk, relying first on a cane, then on a wheelchair. The singer and actress eventually lost her ability to talk and Annette faded from public view.

Many fans still wonder what happened to the beloved Hollywood star.

Now in a world exclusive Annette is back in the public eye. Glen Holt, her husband, invited W5 into their home to show the devastating effects of chronic progressive multiple sclerosis and to talk about a new controversial treatment which he says has helped his wife.

“When she got diagnosed … I told her, ‘I will take care of you and I`ll do everything I can,’” says Glen who is now 81 years old and her primary caregiver.

Annette receives around-the-clock care. She is fed through a tube and must be carried from her bed to her wheelchair.

Her long-term friend Shelley Fabares says seeing Annette today will be shocking to some but necessary to truly understand the effects of her illness.

“There are some people who will think she must be preserved in people’s minds exactly as she was. But exactly who she was is not who she is now,” she explains. “In order to get people to understand the ravages of this disease and what happens…there is no better way.”

Despite her condition Glen never gave up hope that Annette would improve one day.

So when he received a fan letter from an MS patient about a novel and highly controversial treatment he vowed to learn more.

He researched a condition called Cerebrospinal Venous Insufficiency or CCSVI. The disorder was discovered by Italian vascular surgeon Dr. Paulo Zamboni, who believes MS patients have narrowed or blocked jugular and azygous veins that prevent blood from draining from their brains and spinal cords. His theory suggests the blood flows back into the brain, triggering an immune response which eventually leads to the damage seen in MS.

Dr. Zamboni`s treatment involves opening up the blocked veins with a balloon to improve drainage. In a published study his MS patients reported a reduction in MS symptoms after receiving the therapy. It was dubbed the Liberation Treatment.

But Zamboni’s theory contradicts conventional belief that MS is an autoimmune disease triggered by a defective immune system. Neurologists criticized Zamboni’s results saying they were unscientific and his study was too small and hard to replicate.

When other researchers conducted their own studies on CCSVI, the results were inconclusive. Some show no link between CCSVI and MS at all, or found the blocked veins in healthy people. Yet other research suggest the therapy reduces MS symptoms and improves quality of life. The medical debate soon erupted into a war, pitting patients against doctors and physicians against each other.

And yet, Glen was hopeful.

He spent 25 years trying other experimental treatments -- a surgery to implant electrodes in her brain to control her tremors, even an experimental drug that sent Annette into ICU for eight days. But nothing helped.

Glen figured if CCSVI could make one small bit of difference it was worth a shot. He ran the idea by Annette’s long-time doctor Jeffrey Salberg.

“I told him it was something I had not heard of,” he says. “And exploring more information from people who were actually doing the procedure, finding out their academic and their reputations, I started having a little bit more confidence in the idea that it might be worth trying.”

Glen then took Annette to Dr. Donald Ponec, an interventional radiologist at Tri City Hospital in Oceanside, Calif., who had some experience with the new therapy.

Dr. Ponec conducted a study published in August in the Journal of Vascular and Interventional Radiology that followed 259 patients with MS. The researchers used balloons to open up their narrowed veins. After six months, 53.6 per cent of the patients reported improvements in MS symptoms.

In September 2011 at a private clinic, Dr. Ponec tested Annette and found her results fit the new theory. She had a blocked right jugular vein with only 30 per cent blood flow. Her left vein was completely blocked. The blood was flowing back into her brain.

There was no proof that the treatment would even improve her condition but Glen asked doctors to try.

He was in the procedure room with Annette’s nurses -- and says he saw improvements right away when doctors opened up blockages with a balloon and used a stent for a vein.

“When they started the procedure she looked more alive. She was brighter than she was before.”

“I saw in front of my eyes things changed -- the glow of her face came in,” he says.

But Glen says there was another noticeable improvement. Patients with MS often have problems swallowing because of damage to parts of their brain, causing them to sometimes choke on their own saliva.

Before the treatment Glen says he would be awake several hours through the night to suction saliva from Annette’s mouth so she would not suffocate. Now she can get through the night without his help.

Annette’s doctor Dr. Jeffrey Salberg initially did not see changes.

“Glen perceives there are changes day to day. I mean, I cannot see them to be honest , but remember she has had this damage for a long, long time and it has done terrible things to her nervous system and that damage cannot be undone,” said Dr. Salberg.

“You have a scarred, injured brain, how much does venous flow change the function of what is left? I don`t see tremendous changes. But Glen sees little changes and I`m hoping that`s real for him and for her and gives them some sense that it was worth doing.”

That was in October 2012. But in early March this year, Annette had a six-month follow up visit with Dr. Salberg. This time he tells W5 he saw “heartening” improvements in her condition.

In an email to CTV/W5, Dr. Salberg confirms that Annette was attempting to respond to questions by blinking on command and with facial reactions.

“She seemed much more responsive to my verbal conversation with her. She made clear eye contact with me, suggesting improvement in both her vision and cognition that had been damaged by the severity of her chronic progressive MS. She clearly was trying to respond affirmatively to yes and no questions with appropriate facial movements. I have not seen this degree of attentiveness and responsiveness by her in years.”

“While MS can certainly fluctuate in its severity …. it is hopeful that the improvements noted by Glen, and now myself may suggest some clinical benefit to Annette from the procedure” wrote Dr. Salberg.

Glen has always maintained there were improvements following the angioplasty.

"I see changes. And you know to me when you can see some changes like they always say, where there is smoke there is fire,” says Glen. “I see something that`s very positive and it needs to be researched further.”

So he decided to go public with their story. Glen believes Annette`s loyal fans will send money to the Annette Funicello Foundation for Neurological Disease for new CCSVI research and how blood flow impacts other brain diseases. He is a newcomer to social media, but he will soon be posting news about Annette`s condition a couple of times a week. There are also plans for a Twitter account, an account on Facebook and an Annette Funicello YouTube channel to reach out to her fans around the world.

“I think to some degree he just thinks it`s time, time to speak out and to try and raise money to become a new voice...I see that as what he`s doing now. He wants to use her fame and popularity to move things in a new direction,” said Dr. David Hubbard, a neurologist who sits on the board of Annette`s foundation.

Glen’s support is coming at a critical time.

CCSVI Research slowed to a crawl after the U.S. Food and Drug Administration FDA issued a warning about the treatment in May, stating ``there is no reliable evidence ....this procedure is effective in treating MS`` and the procedure using balloons to open up veins `` poses a risk to patients`` and researchers who want to study CCSVI must get FDA approval.

But Dr. Ponec believes the CCSVI theory raises important questions and says funding more research is the only way to find out if CCSVI treatment can help MS patients. Until there is a proper clinical trial that answers the question once and for all -- the debate will rage on, he insists.

“It is the type of research that somebody has to be devoted enough to put money behind it and really try to understand it….there are people in the United States and around the world who are willing to do it, they want to do it. Now I think we need people like Glen or others to help get it going,” he says.

“We`re going to use Annie`s name, yes. And it`s not going to be used in vain, we`re going to do something with it,” insists Glen.

“I want to touch their hearts so they will go out there and help us raise some money,” says Glen. ``I going to continue to fulfill her wish that to help find a cause and a cure.`

Photos

Annette Funicello was the most popular 'Mouseketeer' on 'The Mickey Mouse Club' television show, attracting fans all around the world. She developed into a stunning young woman, starring in several iconic beach movies with teen heartthrob Frankie Avalon.

Annette went public with the news that she had multiple sclerosis in 1992 at the age of 50. She had the most severe form of the disease and over the years lost her ability to walk, relying first on a cane, then on a wheelchair.

Annette Funicello's husband Glen Holt is now her primary caregiver. Annette receives around-the-clock care, is fed through a tube and must be carried from her bed to her wheelchair.

Cerebrospinal Venous Insufficiency, or CCSVI, was discovered by Italian vascular surgeon Dr. Paulo Zamboni, who believes MS patients have narrowed or blocked jugular and azygous veins that prevent blood from draining from their brains and spinal cords.

Dr. Jeffrey Salberg, Annette Funicello's long-time doctor, says Annette’s improvements following the Liberation Treatment may be in the eye of the beholder.